Exposure of humans to sunlight produces adaptive and pathological responses in the skin, including erythema (inflammation), tanning, photoaging, photoallergy and carcinogenesis. These responses involve the modulation of gene expression and excessive exposure can result in mutation and tumorigenesis. The effects produced by ultraviolet radiation (UVR) can be modulated by a number of chemicals applied topically or systemically. The proposed research will explore the use of engineered human skin (EHS), an in vitro model possessing a dermis and differentiated epidermis, to evaluate chemical agents that modulate UVR-induced responses in skin. Initial studies (Phase I) will focus on proof-of-concept using EHS and gene expression technology to identify a set of genes that undergo modulation in response to exposure to simulated sunlight. Follow-on research (Phase II) will validate the model using a defined set of known chemical modulators of UVR-induced skin damage and will extend these studies to the use of EHS incorporating adnexal specialized cell types, e.g. melanocytes and Langerhans cells. Gene expression will be monitored after single and multiple exposures to UVR. Identification of gene expression biomarkers will allow the development of reagents or processes to screen for protective or deleterious effects of chemical agents on UVR-exposed EHS, potentially reducing the need for assays using experimental animals or human subjects. PROPOSED COMMERCIAL APPLICATION: The proposed research utilizes engineered human skin (an in vitro model possessing a dermis and differentiated epidermis) and gene expression technology to identify a set of genes that undergoes modulation in response to exposure to ultraviolet radiation (UVR). Identification of such biomarkers will allow the development of reagents or processes to screen for protective or deleterious effects of chemical agents on UVR exposed human skin, potentially reducing the need for assays using experimental animals or human subjects.